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The V89L Polymorphism in the 5-Reductase Type 2 Gene and Risk of Prostate Cancer¹

Lank Center for Genitourinary Oncology, Department of Adult Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115 [P. G. F., P. W. K., D. C., S. B.]; Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Physician’s Health Study, Harvard School of Public Health, Boston, Massachusetts 02115 [C. H. H.]; Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Physician’s Health Study, Harvard School of Public Health, Boston, Massachusetts 02115 [E. G.]; and Departments of Epidemiology and Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115 [E. G., C. H. H., M. J. S.]

5-Reductase type 2, the predominant prostatic isozyme of this protein, converts testosterone to dihydrotestosterone. It has been hypothesized that individuals with greater 5-reductase activity are at increased risk for prostate cancer (CaP). A single nucleotide polymorphism of the 5-reductase type 2 gene (SRD5A2) gives rise to a substitution of leucine (leu) for valine (val) at codon 89 (V89L), the presence of which may affect serum androstanediol glucuronide (AAG) levels. We studied the effect of this polymorphism on the risk of prostate cancer in a prospective, nested, case-control design within the Physicians’ Health Study. In all controls (n = 799), the leu allele frequency was 0.30. Among the 386 controls with plasma AAG levels available, there was no significant association between AAG levels and V89L genotype. We also detected no significant association between risk for CaP and genotype [odds ratio: val/val = 1.0 (reference), leu/val = 0.96 (95% confidence interval, 0.76–1.20), and leu/leu = 0.84 (95% confidence interval, 0.57–1.24)]. These data do not support a moderate to large effect of the SRD5A2 V89L polymorphism on plasma AAG levels or CaP risk in this predominantly Caucasian cohort, although a small effect cannot be completely excluded.

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